Scope of Work Problem: South Africa, particularly the Western Cape, has experienced a dramatic rise in methamphetamine use over the past decade and also has the largest number of HIV-infected individuals (5.3 million) of any country in the world. It is feared that methamphetamine use may further fuel this HIV epidemic because of its association with risky sexual behaviors. Despite widespread concern about methamphetamine, there has been limited research examining the intersection of the methamphetamine and HIV epidemics in South Africa. Aims: The primary purpose of this exploratory study is to characterize the patterns and severity of drug use among methamphetamine users in Cape Town, and to identify the multiple levels of influence on HIV sexual risk behavior in this population (Aims 1 and 2). We will apply Ecological Systems Theory, which views behavior as reciprocally influenced by factors from the individual, social, environmental, and community levels, as an organizing framework for this research. A secondary purpose is to test the feasibility of using respondent driven sampling (RDS) to recruit methamphetamine users for future HIV prevention studies (Aim 3). Method: Following a phase of formative research to inform the recruitment strategy and pilot test the assessment battery, we will use a chain referral approach to enroll a convenience sample of 160 male and female methamphetamine users from a township in Cape Town for a multi-method study. All participants will complete a quantitative survey that assesses patterns of methamphetamine use and history of substance abuse treatment; rates of sexual risk behavior and use of HIV-related services; and correlates of sexual risk behavior at multiple levels of influence. A sub-sample of 30 participants will be selected for in-depth qualitative interviews to explore patterns of methamphetamine use, progression from casual use to addiction, and the social context of drug use; how methamphetamine use contributes to sexual risk behavior; and barriers and facilitators to drug cessation and treatment, safer sex practices, and HIV testing. Finally, we will test the feasibility of using RDS to enroll methamphetamine users in Cape Town into future HIV prevention research by conducting formative research to determine the suitability and acceptability of this recruitment method and to calibrate the method for this population, and by analyzing the chain referral data to determine whether RDS requirements are met. Significance: This timely proposal, among the first to target methamphetamine users in South Africa, will advance the field of HIV prevention by examining how methamphetamine use may contribute to HIV sexual risk behavior in a sample of non-injecting and primarily heterosexual drug users. The goal of the proposed research is to identify key factors that will inform the development of integrative prevention interventions to reduce methamphetamine use and sexual risk behaviors in the population. PUBLIC HEALTH RELEVANCE: Methamphetamine is the second most widely abused drug in the world (after marijuana), and it is associated with higher rates of sexual risk behavior and HIV infection. South Africa has experienced a dramatic increase in methamphetamine use in recent years and has the largest number of HIV-infected individuals of any country in the world. This multi-method study will characterize the patterns and severity of drug abuse among methamphetamine users in South Africa and will identify multiple levels of influence on HIV sexual risk behavior in this population to inform the development of integrative prevention interventions to improve access to HIV-related services and reduce the continued spread of the HIV virus.